Science - April 21, 2011

Down to the last nanometre

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Nano technology increasingly means bionano, and that is why Wageningen UR has come in for a big share of the millions of euros in grants from NanoNextNL. Research on topics ranging from computer chips with a layer of sugar, perfecting microcapsules of vitamins, and the risks associated with nanoparticles. Studying the nano level, says Professor Han Zuilhof, 'You are looking at something so small it's almost non-existent.'

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Twenty million euros for nano- and micro-level technical research on nutrition, materials, sensors and risks. The financial overview on the wall of Professor of Organic Chemistry Han Zuilhof's office shows the figures. Almost ten million comes from the NanoNextNL programme; eight million is put in by Wageningen UR, in the form of staff and equipment.
Nanotechnology is more readily associated with the Netherlands' three technical universities than with Wageningen UR. According to Zuilhof, who coordinates the programme within Wageningen UR, that idea is wide of the mark. Zuilhof was previously involved in the predecessors of NanoNext, NanoNed and MicroNed, both projects in which Wageningen played a significant role. And now once again, Zuilhof is the biggest participant.
Wageningen is doing well, says Zuilhof, thanks to its capacity to combine fundamental research with knowing what sorts of applications industry wants. 'Traditionally, the three technical universities come out on top in the technological programmes. And when it comes to fundamental research, the big universities such as Utrecht stand out - they have very large staffs. But in NanoNext you need high-quality fundamental research while at the same time making sure that the participating industry commits itself to an equal level of funding. And apparently we are very good at that in Wageningen.'

Thousands on the space of a fingernail
Zuilhof's expertise is in the field of bioactive molecules such as complex sugars and their chemical bonding to everyday surfaces. One of the eight projects in which Zuilhof's group is participating is a collaboration with professor of Microbiology Willem de Vos and the company Microdish. Microdish developed a bacteria breeding chip which can breed bacteria on miniscule breeding surfaces - thousands on a surface the size of one fingernail - so as to be able to count and identify them. Zuilhof: 'We want to modify that breeding substratum so that it binds one species of bacteria to it, but not others. Then you can preselect them and make the test much more sensitive.' He aims to do this by attaching saccharides or antibodies to the surface. 'This layer is only two nanometres thick, exactly the thickness of a molecule.'
As a result, a great deal of effort is going into research on this nano-layer. Zuilhof: 'In nano technology you see a lot of nice presentations with beautiful graphs, which suggest how a molecule stays on a surface. But if you really want to demonstrate what is on it, there are often a few natural laws that get in between your dream and carrying it out.ยด
An Auger electron spectroscope that cost 600,000 euros does deliver the needed evidence. Using this microscope, which has been in the lab for a year now, a surface of 30 by 20 nanometres and two nanometres deep can be studied. Zuilhof: 'You are looking at something so small it's almost non-existent. But only then can I tell what is on it.' Zuilhof sees his 'car park' as one of the reasons why his group attracts so many research projects. 'We are extremely well-equipped.'

Microfluidics
Another nano project focuses on microfluidics: chemical reactions and fluid flows in a glass flow reactor the size of a business card, through which the various ingredients flow towards each other down channels of between ten and 100 micrometres in size. Through these channels it is possible to make emulsions of oil and water with a very uniform droplet size of 10 micrometres. 'Under the microscope, the droplets that come out look like perfect, evenly proportioned marbles. We want to improve on this and make complex structures - balls within balls, for example. Other microstructuring research in Boom's group looks at the formation of protein fibres. Atze-Jan van der Goot has been doing intensive research for years on the structuring of proteins for meat substitutes. 'In meat, bread and cheese, the structures at the nano scale determine the characteristics of the micro scale', says Van der Goot. The way in which gluten or muscle protein forms a network determines the firmness of bread or the tenderness of meat.
'We always start from existing food ingredients and proteins and try to manipulate their structures', says Van der Goot. That is an important criterion for the food industry, as anyone developing really innovative new ingredients will have to get them through the test of complicated European Novel Food rules and acceptance procedures.
'What is more, the industry is interested in microstructuring, and people are a bit wary of the term nanotechnology in combination with food, as it conjures up associations with nanoparticles.' 

Growth-inhibiting nanosilver
Nanoparticles represent the more controversial side of nanotechnology. There have been warnings in recent years, mainly from civil society organizations, about hidden risks for people and the environment. A particular focus of concern is carbon nanotubes, because they resemble asbestos fibres, and may carry similar risks of causing lung cancer. Carbon nanotubes have no applications in consumer products, but nanosilver particles do: they can be used in clothing and packaging and as a growth inhibitor for bacteria. Nanosilica can be used as an anticoagulant in milk powder, titanium oxide particles can be used to obtain self-cleaning surfaces in paints, and UV-absorbing zinc oxide particles are used in sun creams.
The question is whether these special characteristics of nanoparticles can have negative impacts on the environment or on people and animals that ingest them.
'But once they are part of a food matrix or in the digestive tract, you can no longer compare their characteristics with those of the pure nanoparticles the manufacturer used', says RIKILT researcher Hans Bouwmeester, who does toxicological research in NanoNext. 'So you have to show what the characteristic of the particles are in the matrix you are studying. The issue is whether they are freely available, whether they can pass through barriers such as lungs and intestines. And if so, where do they end up? We do not really know yet what we should be looking at in toxicological research on nanoparticles: DNA damage, damage to mitochondria or damage to the immune system?'

Interdisciplinary
Research on biological interactions with nanoparticles is one of the reasons, says Bouwmeester, why Wageningen scored so well for funding. 'After all, that is something the hard technologists at Delft and Twente are not as good at.'
Zuilhof concurs with this. 'In the nano sciences, we are hearing the word bio more and more often, because that is where the interesting applications are. Nowadays I read The Cell because I can see that we shall have to go in that direction. And why are external parties so keen to work with us? Because in Wageningen UR we have chemists, process technologists, molecular biologists and microbiologists. And these people have been working together for some time, so that gives us a very strong position in nano research.'
/Arno van 't Hoog
NanoNextNL
NanoNextNL supports research in the field of nano and microtechnology to the tune of 250 million euros, half of which comes from the government and the other half from companies and knowledge institutions. The programme is a follow-up to two earlier grant programmes, NanoNed and MicroNed.
NanoNextNL has 27 programmes, three of which are led by a Wageningen director. Remco Boom professor of Food Process Engineering, is leading the nutrition programme, Maarten Jongsma from PRI is responsible for the Food Diagnostics programme and Han Zuilhof leads the Biosending & Microstructures programme. Zuilhof's group will be spending 6.5 million euros on its research over the next five years. Remco Boom is responsible for the second largest budget at well over one million euros. Other participating research groups are those of Erik van der Linden, Ivonne Rietjens, Martien Cohen Stuart and Nico van den Brink.

Nano and micro
A nanometre is one billionth of a metre, while a micrometre is one millionth of a meter. To get some idea what we are talking about: a human hair is between 60,000 and 80,000 nanometres thick. A glucose molecule is about 1 nanometre long, and a DNA molecule is about 2.5 nanometres thick.
Nanotechnology entails the study, production and application of molecular structures and materials that range in size from a few dozen to hundreds of nanometres. They might be biological molecules such as those of DNA, lipids or proteins. Or they could be liposomes, clay particles or metal particles.

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